Bayesian optimization (BO) is regarded as an efficient approach that can identify optimal conditions using a restricted number of experiments. Despite demonstrated potential of BO, applications of BO‐based approaches in synthetic organic chemistry remain limited. Herein, we achieved the first rapid and mild (5.1 s, 20 °C) one‐flow synthesis of unsymmetrical sulfamides from inexpensive sulfuryl chloride. Undesired reactions were successfully suppressed and the risk in handling sulfuryl chloride was minimized by the use of micro‐flow technology. The reaction conditions producing ≥75 % yield were identified by a machine learning approach based on BO. It was demonstrated that BO produced the desired reaction conditions with a small number of experiments (19 and 10 experiments) in the entire search space (10,500 combinations of reaction conditions). Gaussian process (GP) models produced by BO provided the relationships between combinations of reaction parameters and outputs (RCRPO).
b-Amino acid N-carboxy anhydrides (b-NCAs)a re rarely used in the synthesis of b-peptides, which is due mainly to the poor availability of these potentially useful substrates. Herein, we describe the heretofore challenging synthesis of b-NCAs via as ingle-step, rapid, and mild formation using pH flash switchinga nd flash dilution, which are aspects of micro-flow technology.W es ynthesized 15 b-NCAs in good to excellent yields that included acid-labile b-NCAs that cannotb er eadily synthesized using the conventional Leuchsa pproach. Scaled-up synthesis using this process can be readily achievedv ia continuous operation.
Thirty compounds in the volatile fraction of McIntosh apple juice were isolated and identified. Material for gas chromatography was prepared by concentrating volatiles tenfold in a rising film evaporator and extracting with ethyl chloride. The compounds were identified by comparing retention volumes and infrared spectra with those of known compounds. Volatile components tentatively identified on the basis of their infrared spectra and retention data included 4 aldehydes, 1 ketone, 11 alcohols, 10 esters, and 4 fatty acids. In addition, 7 peaks were found but not identified. A variety of column packings and operating conditions were necessary to obtain reasonable separation of the components isolated.
Developments that result in high-yielding, low-cost, safe, scalable, and less-wasteful processes are the most important goals in synthetic organic chemistry. Continuous-flow reactions have garnered much attention due to many advantages over conventional batch reactions that include precise control of short reaction times and temperatures, low risk in handling dangerous compounds, and ease in scaling up synthesis. Combinations of continuous-flow reactions with homogeneous, metal-free catalysts further enhances advantages that include low-cost and ready availability, low toxicity, higher stability in air and water, and increased synthetic efficiency due to the avoidance of the time-consuming removal of toxic metal traces. This review summarizes recently reported continuous-flow reactions using metal-free homogeneous catalysts and classifies them either as acidic catalysts, basic catalysts, or miscellaneous catalysts. In addition, we compare the results between continuous-flow conditions and conventional batch conditions to reveal the advantages of using flow reactions with metal-free homogeneous catalysts.
A variety of urethane-protected α-amino acid N-carboxyanhydrides (UNCAs) were synthesized in high yields via the rapid dual activation of both an α-NCA and alkyl chloroformate by combination of two amines in a micro-flow reactor.
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